EP0165669A1 - Méthode pour la mesure de ligand libre - Google Patents
Méthode pour la mesure de ligand libre Download PDFInfo
- Publication number
- EP0165669A1 EP0165669A1 EP85302538A EP85302538A EP0165669A1 EP 0165669 A1 EP0165669 A1 EP 0165669A1 EP 85302538 A EP85302538 A EP 85302538A EP 85302538 A EP85302538 A EP 85302538A EP 0165669 A1 EP0165669 A1 EP 0165669A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- ligand
- labeled
- labeled ligand
- free
- derivative
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000003446 ligand Substances 0.000 title claims abstract description 85
- 238000000034 method Methods 0.000 title claims description 31
- 239000002981 blocking agent Substances 0.000 claims abstract description 20
- 239000011230 binding agent Substances 0.000 claims abstract description 15
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 claims description 31
- XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 claims description 30
- 229940034208 thyroxine Drugs 0.000 claims description 24
- 102000014914 Carrier Proteins Human genes 0.000 claims description 19
- 108091008324 binding proteins Proteins 0.000 claims description 19
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 claims description 16
- 239000007788 liquid Substances 0.000 claims description 13
- 239000005495 thyroid hormone Substances 0.000 claims description 13
- 229940036555 thyroid hormone Drugs 0.000 claims description 13
- 239000006274 endogenous ligand Substances 0.000 claims description 12
- 238000005259 measurement Methods 0.000 claims description 9
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- 108090000623 proteins and genes Proteins 0.000 claims description 8
- 239000006277 exogenous ligand Substances 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 6
- AUYYCJSJGJYCDS-UHFFFAOYSA-N 2/3/6893 Natural products IC1=CC(CC(N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-UHFFFAOYSA-N 0.000 claims description 5
- 231100000673 dose–response relationship Toxicity 0.000 claims description 2
- 230000005298 paramagnetic effect Effects 0.000 claims description 2
- 239000007790 solid phase Substances 0.000 claims 3
- 239000007791 liquid phase Substances 0.000 claims 2
- 239000012086 standard solution Substances 0.000 claims 1
- 238000003556 assay Methods 0.000 abstract description 14
- 238000003018 immunoassay Methods 0.000 abstract description 9
- 239000000523 sample Substances 0.000 description 20
- 229960001860 salicylate Drugs 0.000 description 12
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 12
- 241000894007 species Species 0.000 description 9
- 210000002966 serum Anatomy 0.000 description 7
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 6
- 102000002248 Thyroxine-Binding Globulin Human genes 0.000 description 6
- 108010000259 Thyroxine-Binding Globulin Proteins 0.000 description 6
- 229960004025 sodium salicylate Drugs 0.000 description 6
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 5
- 239000013060 biological fluid Substances 0.000 description 5
- 239000000700 radioactive tracer Substances 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 229940098773 bovine serum albumin Drugs 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000000502 dialysis Methods 0.000 description 4
- 229960002036 phenytoin Drugs 0.000 description 4
- 108010088751 Albumins Proteins 0.000 description 3
- 102000009027 Albumins Human genes 0.000 description 3
- 102000004506 Blood Proteins Human genes 0.000 description 3
- 108010017384 Blood Proteins Proteins 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000013610 patient sample Substances 0.000 description 3
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 3
- 108010071690 Prealbumin Proteins 0.000 description 2
- 102000007584 Prealbumin Human genes 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- -1 i.e. Proteins 0.000 description 2
- 230000002452 interceptive effect Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 229960002895 phenylbutazone Drugs 0.000 description 2
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 229960004906 thiomersal Drugs 0.000 description 2
- NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 1
- BGHIEJHQLIHWPX-UHFFFAOYSA-N 3-[(4-anilinonaphthalen-1-yl)diazenyl]naphthalene-2,7-disulfonic acid Chemical compound OS(=O)(=O)C1=CC2=CC(S(=O)(=O)O)=CC=C2C=C1N=NC(C1=CC=CC=C11)=CC=C1NC1=CC=CC=C1 BGHIEJHQLIHWPX-UHFFFAOYSA-N 0.000 description 1
- FWEOQOXTVHGIFQ-UHFFFAOYSA-N 8-anilinonaphthalene-1-sulfonic acid Chemical compound C=12C(S(=O)(=O)O)=CC=CC2=CC=CC=1NC1=CC=CC=C1 FWEOQOXTVHGIFQ-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000736355 Euthyroides Species 0.000 description 1
- KNAHARQHSZJURB-UHFFFAOYSA-N Propylthiouracile Chemical compound CCCC1=CC(=O)NC(=S)N1 KNAHARQHSZJURB-UHFFFAOYSA-N 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 102000009488 Thyroxine-Binding Proteins Human genes 0.000 description 1
- 108010048889 Thyroxine-Binding Proteins Proteins 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical compound C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 description 1
- 229960005426 doxepin Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- PMRYVIKBURPHAH-UHFFFAOYSA-N methimazole Chemical compound CN1C=CNC1=S PMRYVIKBURPHAH-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- WIKYUJGCLQQFNW-UHFFFAOYSA-N prochlorperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 WIKYUJGCLQQFNW-UHFFFAOYSA-N 0.000 description 1
- 229960003111 prochlorperazine Drugs 0.000 description 1
- 229960002662 propylthiouracil Drugs 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 229960002178 thiamazole Drugs 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/5306—Improving reaction conditions, e.g. reduction of non-specific binding, promotion of specific binding
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54393—Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
- G01N33/78—Thyroid gland hormones, e.g. T3, T4, TBH, TBG or their receptors
Definitions
- the present invention relates to the measurement of free ligand in a liquid sample which contains the ligand in both free and bound states. More particularly, the present invention relates to. an improvement in the measurement of free ligand in a liquid sample which contains the ligand in both free and combined states.
- each species typically is bound to one or more endogenous proteins, i.e., proteins which are normally present in the biological fluids. There often is a single protein which is primarily responsible for such binding.
- the amount of a given species which is present in the free state usually represents only a very small percentage of the total amount of the species present in the biological fluid and typically is more significant clinically than the total amount of the species or the amount of the species which is present in the bound state. There are times, however, when it is either desirable or necessary to know both the amount of the species which is present in the free state and the total amount of the species present in the biological fluid.
- thyroid hormones e.g., thyroxine and 3,5,3'-triiodothyronine.
- thyroxine and 3,5,3'-triiodothyronine Approximately 99.97% of the thyroxine and About 99.7% of the 3,5,3'-triiodothyronine in human serum are bound to endogenous serum proteins, especially thyroxine binding globulin (TBG).
- TBG thyroxine binding globulin
- U.S. Patent No. 4,046,870 discloses a method for determining the concentration of free thyroid hormone in a blood serum sample, which method comprises the steps of analyzing the sample via immunoassay techniques for either thyroid hormone in the presence and absence of a blocking agent to establish a thyroid hormone binding differential and then correlating that differential with a standard curve relating the respective free thyroid hormone concentrations to binding differentials.
- the blocking agent typically was thiomersal at a concentration of 2.5 mg/ml.
- the immunoassay carried out in the presence of a blocking agent gives a result which can be correlated with the total thyroid hormone concentration through the use of an appropriate dose-response or standard curve.
- the procedure is especially advantageous when it is necessary or desirable to know both free and total thyroid hormone concentrations.
- the procedure still requires two separate measurements. Consequently, such procedure often has been deemed less desirable than one in which a single measurement is required for the determination of free thyroid hormone.
- Yet another object of the present invention is to provide an improved single step free ligand immunoassay.
- Still another object of the present invention is to provide an improved single step free ligand immunoassay which is more diagnostically specific and has fewer false positives in the hypothyroid range than prior art single step free ligand immunoassays.
- the present invention provides, in a method of determining the concentration of a free ligand in a liquid sample which contains the ligand in both free and bound states, which method comprises the steps of:
- the ligand is a thyroid hormone, such as thyroxine or 3,5,3'-triiodothyronine.
- the specific binder is immobilized on a water-insoluble support.
- the water-insoluble support is particulate and, optionally, paramagnetic.
- endogenous ligand binding proteins includes those ligand binding proteins which are naturally present in a given biological sample.
- exogenous ligand binding proteins includes those proteins which are added to the sample during either sample preparation or the assay procedure and which are capable of at least partially binding the labelled ligand or labelled ligand derivative.
- many free thyroxine assay procedures require the addition of bovine serum albumin to the sample.
- bovine serum albumin typically is capable of at least partially binding the labelled thyroxine or labelled thyroxine derivative employed in the assay.
- exogenous ligand binding proteins are similar to the endogenous ligand binding proteins in their affinity for labelled ligand or labelled ligand derivative.
- specific endogenous ligand binding protein refers to the endogenous protein which is primarily responsible for binding ligand.
- the specific endogenous thyroxine binding protein is thyroxine-binding globulin (TBG).
- the blocking agent can be any compound which serves to prevent significant binding of the labeled ligand to endogenous and/or exogenous ligand binding proteins.
- Suitable blocking agents include, among others, 8-anilino-l-naphthalenesulfonic acid, 3-(4-anilino-1-naphthylazo)-2,7-naphthalenedisulfonic acid, 2,4,6-trinitrobenzenesulfonic acid, ⁇ -naphthalenesulfonic acid, sodium ethylmercurithiosalicylate (thiomersal) , sodium salicylate, phenytoin (diphenylhydantoin or 5,5-diphenyl-2,4-imidazolidinedione), doxepin, diazapam, prochlorperazine, phenylbutazone, propylthiouracil, methimazole, and the like.
- the blocking agent is employed in an amount which is sufficient to prevent significant binding of the labeled ligand or labeled ligand derivative to endogenous and/or exogenous ligand binding proteins without causing significant release of bound ligand. Such amount will vary, depending upon the blocking agent and the labeled ligand or labeled ligand derivative, among other factors. However, one having ordinary skill in the art can readily determine- such amount without undue experimentation.
- the amounts of blocking agents employed in U.S. 3,911,096 varied from 50 ug to 10 mg per 25 ul of serum, which amounts displaced from 3.0 to greater than 20 ng of thyroxine from TBG.
- Human serum normally contains-no more than about 12.5 ug of thyroxine per dl, which amount corresponds to about 3.1 ng per 25 ⁇ l sample.
- all of the blocking agents were employed in amounts which released at least 3.1 ng of thyroxine from TBG.
- sodium salicylate was suitably employed in a free thyroxine radioimmunoassay at a concentration of 0.375 g/l in the tracer solution. Since the amount of tracer solution utilized was 200 ⁇ l and the sample size was 50 ⁇ l, the amount of sodium salicylate per 25 ⁇ l of sample would be 37.5 pg. In U.S. 3,911,096, however, sodium salicylate was tested at a level of 10 mg per 25 ul of sample, a 267-fold increase over the level employed in the Examples.
- the method of the present invention is useful in any single step free ligand immunoassay which utilizes a labeled ligand or labeled ligand derivative which is substantially nonreactive with binding proteins present in the sample, irrespective of the particular protocol employed.
- Table II The data presented in Table I were treated to statistical analysis in two groups: (1) samples which also were analyzed by equilibrium dialysis and (2) all samples. The statistical analyses are summarized in Table II.
- Example 1 The procedure of Example 1 was repeated, except that the samples employed represented abnormal patient populations.
- the data are summarized in Tables I II through XII.
- Example 1 The procedure of Example 1 was followed, except that the patient samples represented sick euthyroid patients.
- the data are presented in Tables XIV and XV.
- Table XIV summarizes patient diagnoses
- Table XV summarizes the results of the single tube free thyroxine assay without and with the addition of salicylate to tracer reagent.
- Example 1 The procedure of Example 1 was repeated once more, this time on patient samples taken before and after dialysis.
- the data are summarized in Tables XVI and XVIII.
- the number of patients within the normal range when assayed without and with salicylate are 6 and 7, respectively, while the percent diagnostically correct are 75 and 87.5, respectively.
- the number of patients within the normal range when assayed without and with salicylate are 1 and 6, respectively, a significant improvement resulting from the use of salicylate.
- the percent diagnostically correct without and with salicylate are 12.5 and 75, respectively.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Endocrinology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US60714884A | 1984-05-04 | 1984-05-04 | |
| US607148 | 1984-05-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP0165669A1 true EP0165669A1 (fr) | 1985-12-27 |
Family
ID=24431024
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP85302538A Withdrawn EP0165669A1 (fr) | 1984-05-04 | 1985-04-11 | Méthode pour la mesure de ligand libre |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP0165669A1 (fr) |
| JP (1) | JPS60249056A (fr) |
| CA (1) | CA1305410C (fr) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0218309A2 (fr) * | 1985-10-04 | 1987-04-15 | Diagnostic Products Corporation | Procédé pour déterminer les ligands libres dans les fluides biologiques |
| FR2598514A1 (fr) * | 1986-05-12 | 1987-11-13 | Commissariat Energie Atomique | Procede de dosage immunologique des hormones thyroidiennes t3 et/ou t4 utilisant la thyroglobuline |
| WO1988009505A1 (fr) * | 1987-05-21 | 1988-12-01 | P B Diagnostic Systems, Inc. | Systeme d'analyse diagnostique biologique |
| AU601993B2 (en) * | 1986-07-19 | 1990-09-27 | Boehringer Mannheim Gmbh | Process and agent for the detection of an analyte |
| US5198340A (en) * | 1991-01-17 | 1993-03-30 | Genentech, Inc. | Assay for free igf-i, igf-ii, and gh levels in body fluids |
| EP0535239A1 (fr) * | 1991-03-18 | 1993-04-07 | Shiseido Company Limited | Procede et materiel de dosage de collagene |
| US6159698A (en) * | 1996-07-18 | 2000-12-12 | Dade Behring Marburg Gmbh | Reagents for assays for mycophenolic acid |
| US6171801B1 (en) | 1996-07-18 | 2001-01-09 | Dade Behring Marburg Gmbh | Methods for releasing a ligand from a complex |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5364796A (en) * | 1989-07-11 | 1994-11-15 | Pb Diagnostics Systems, Inc. | Diagnostic assay system |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3911096A (en) * | 1972-06-23 | 1975-10-07 | Professional Staff Ass Of The | Radioimmunoassay for measurement of thyroxine (T{HD 4{B ) and triiodothyonine (T{HD 3{B ) in blood serum |
| EP0015687A1 (fr) * | 1979-02-23 | 1980-09-17 | Pharmacia Ab | Détermination de ligands libres |
| EP0078477A2 (fr) * | 1981-11-04 | 1983-05-11 | Miles Laboratories, Inc. | Fenclofenace comme agent inhibiteur dans des essais immunologiques iodothyronine |
| EP0089806A1 (fr) * | 1982-03-22 | 1983-09-28 | AMERSHAM INTERNATIONAL plc | Détermination de la portion libre des substances dans des liquides biologiques |
| WO1983003306A1 (fr) * | 1982-03-19 | 1983-09-29 | Roger Philip Ekins | Procede et composition pour analyses de groupes de coordination libres |
| WO1984001031A1 (fr) * | 1982-08-27 | 1984-03-15 | Roger Philip Ekins | Mesure de la concentration d'un produit |
| EP0133464A1 (fr) * | 1983-07-05 | 1985-02-27 | Miles Laboratories, Inc. | Immunoessai à base d'iodothyronine employant HMS comme agent de blocage pour les TBP |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4018883A (en) * | 1975-03-10 | 1977-04-19 | Nichols Institute For Endocrinology | Thyroxine (T4) radioimmunoassay |
| JPS5886461A (ja) * | 1981-11-04 | 1983-05-24 | マイルス・ラボラトリ−ズ・インコ−ポレ−テツド | 免疫試験用試薬、試験キツト及びそれらを用いる免疫試験法 |
| GB8404843D0 (en) * | 1984-02-24 | 1984-03-28 | Amersham Int Plc | Free analyte assay |
-
1985
- 1985-04-11 EP EP85302538A patent/EP0165669A1/fr not_active Withdrawn
- 1985-05-02 JP JP9532385A patent/JPS60249056A/ja active Pending
- 1985-05-03 CA CA000480717A patent/CA1305410C/fr not_active Expired - Lifetime
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3911096A (en) * | 1972-06-23 | 1975-10-07 | Professional Staff Ass Of The | Radioimmunoassay for measurement of thyroxine (T{HD 4{B ) and triiodothyonine (T{HD 3{B ) in blood serum |
| EP0015687A1 (fr) * | 1979-02-23 | 1980-09-17 | Pharmacia Ab | Détermination de ligands libres |
| EP0078477A2 (fr) * | 1981-11-04 | 1983-05-11 | Miles Laboratories, Inc. | Fenclofenace comme agent inhibiteur dans des essais immunologiques iodothyronine |
| WO1983003306A1 (fr) * | 1982-03-19 | 1983-09-29 | Roger Philip Ekins | Procede et composition pour analyses de groupes de coordination libres |
| EP0089806A1 (fr) * | 1982-03-22 | 1983-09-28 | AMERSHAM INTERNATIONAL plc | Détermination de la portion libre des substances dans des liquides biologiques |
| WO1984001031A1 (fr) * | 1982-08-27 | 1984-03-15 | Roger Philip Ekins | Mesure de la concentration d'un produit |
| EP0133464A1 (fr) * | 1983-07-05 | 1985-02-27 | Miles Laboratories, Inc. | Immunoessai à base d'iodothyronine employant HMS comme agent de blocage pour les TBP |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0218309A2 (fr) * | 1985-10-04 | 1987-04-15 | Diagnostic Products Corporation | Procédé pour déterminer les ligands libres dans les fluides biologiques |
| EP0218309A3 (en) * | 1985-10-04 | 1988-08-31 | Diagnostic Products Corporation | Method for measuring free ligands in biological fluids |
| JPH07311200A (ja) * | 1985-10-04 | 1995-11-28 | Diagnostic Prod Corp | 生物学的液体中の遊離リガンドの測定方法および測定用キット |
| FR2598514A1 (fr) * | 1986-05-12 | 1987-11-13 | Commissariat Energie Atomique | Procede de dosage immunologique des hormones thyroidiennes t3 et/ou t4 utilisant la thyroglobuline |
| EP0246152A1 (fr) * | 1986-05-12 | 1987-11-19 | Cis Bio International | Procédé de dosage immunologique des hormones thyroidiennes T3 et/ou T4 utilisant la thyroglobuline |
| AU601993B2 (en) * | 1986-07-19 | 1990-09-27 | Boehringer Mannheim Gmbh | Process and agent for the detection of an analyte |
| EP0293971A1 (fr) * | 1987-05-21 | 1988-12-07 | PB Diagnostic Systems, Inc. | Système d'essai biologique et diagnostique |
| WO1988009505A1 (fr) * | 1987-05-21 | 1988-12-01 | P B Diagnostic Systems, Inc. | Systeme d'analyse diagnostique biologique |
| US5198340A (en) * | 1991-01-17 | 1993-03-30 | Genentech, Inc. | Assay for free igf-i, igf-ii, and gh levels in body fluids |
| EP0535239A1 (fr) * | 1991-03-18 | 1993-04-07 | Shiseido Company Limited | Procede et materiel de dosage de collagene |
| EP0535239A4 (en) * | 1991-03-18 | 1993-11-18 | Shiseido Company Limited | Collagen assaying method and kit |
| US6159698A (en) * | 1996-07-18 | 2000-12-12 | Dade Behring Marburg Gmbh | Reagents for assays for mycophenolic acid |
| US6171801B1 (en) | 1996-07-18 | 2001-01-09 | Dade Behring Marburg Gmbh | Methods for releasing a ligand from a complex |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS60249056A (ja) | 1985-12-09 |
| CA1305410C (fr) | 1992-07-21 |
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